Adjuvant Docetaxel Fails in Higher-Risk Prostate Cancer

Adjuvant docetaxel without prednisone failed to improve biochemical disease-free survival in men with intermediate- or high-risk prostate cancer who have undergone radical radiotherapy with androgen deprivation therapy, according to results of the Scandinavian Prostate Cancer Group’s multinational phase III SPCG-13 trial.

The findings from SPCG-13 (abstract 5000) were presented by Pirkko-Liisa I. Kellokumpu-Lehtinen, MD, of University of Tampere, Finland at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.

According to Dr. Kellokumpu-Lehtinen, when this trial was planned over 10 years ago chemotherapy was known to be effective in metastatic breast, colorectal, and prostate cancer. However, the survival benefit in castration-resistant prostate cancer was only 2.5 months. At the time, adjuvant chemotherapy was used for breast and colorectal cancers because trials had shown a survival benefit. This trial was designed to answer whether adjuvant chemotherapy after radical radiotherapy for prostate cancer would improve outcome.

In the trial, patients were randomly assigned to either 6 cycles of adjuvant docetaxel at 75 mg/m² every 3 weeks without continuous prednisone (Arm A, n = 187) or to surveillance (Arm B, n = 188). All patients were required to have neoadjuvant/adjuvant androgen deprivation therapy.

Patients were followed for 5 years, with a prostate-specific antigen (PSA) test performed every 3 months for the first 2 years and every 6 months thereafter. The primary endpoint of the trial was rising PSA of 2 ng/mL or more above the nadir PSA value.

The majority of patients (78.2%) completed all of the cycles of docetaxel in Arm A, with only 8 patients receiving no docetaxel at all.

Toxicity was moderate, Kellokumpu-Lehtinen said. Serious side effects related to docetaxel occurred in 52% of patients. Most of these effects were cytopenias, Kellokumpu-Lehtinen said, noting that the researchers obtained blood counts 1 week after administering docetaxel. Febrile neutropenia of any grade occurred in 16.1% of patients. No treatment-related deaths were observed.

During the 5-years follow-up period, no disease progression occurred in 69% of patients in Arm A and 69.7% of patients in Arm B. In the whole study population, the primary endpoint was achieved in about one-third of patients (30.7%), but there was no difference in the primary endpoint between the two study arms.

The biochemical progression rate in both arms at 5-year follow-up was “lower than expected,” Kellokumpu-Lehtinen reported. The Kaplan-Meier curves for biochemical progression-free survival did not separate at all, she said. In univariate and multivariate analyses, Gleason sum was the only predictive factor for progression. T stage or randomization arm did not have a prognostic effect.

A subgroup analysis showed that, for patients with a Gleason score greater than 8, there was a trend favoring docetaxel; however, the P value was not statistically significant (P = .059).

“As we know, docetaxel has shown to be effective in hormone-naive metastatic prostate cancer in the STAMPEDE and CHAARTED trials, but why not in [the adjuvant setting] needs further preclinical and clinical studies,” Kellokumpu-Lehtinen concluded.

Commenting on the findings, Daniel G. Chong, MD, of Virginia Cancer Specialists, Fairfax, Va., said, "While this study demonstrates no DFS benefit when adding docetaxel without prednisone to standard of care ADT plus RT for localized castrate-sensitive prostate cancer, we will need to wait for overall survival results to determine if they correlate with results of the STAMPEDE and RTOG-0521 trials showing that there is benefit to adding chemotherapy in localized prostate cancer."